Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles.

BACKGROUND: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC). METHOD: UFP was measured approximately 2-3 cm from the breathing area of the surgeon (personal sampling) and 3 m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections. The sampling was by P-Trak UFP counter that has the capacity to detect particle size ranging from 0.02 to 1 microm. RESULTS: The cumulative level of UFP of personal sampling in the peritonectomy group was higher (9.3 x 10(6) particle/ml/h (pt/ml/h)) than in the control group (4.8 x 10(5) pt/ml/h). A higher cumulative level of UFP in stationary sampling was observed in the PC group (2.6 x 10(6) pt/ml/h) than in the control group (3.9 x 10(4)pt/ml/h). CONCLUSION: Peritonectomy procedure with high voltage electrocautery generates elevated levels of UFP than standard CRC surgery does. The level of UFP produced by a peritonectomy is comparable to cigarette smoking. More efficient smoke evacuator systems are needed in order to reduce the levels of UFP generated during electrocautery surgery.

Lower serum concentration of matrix metalloproteinase-3 in the acute stage of myocardial infarction.

OBJECTIVES: The importance of matrix metalloproteinases (MMPs) in the progression and rupture of the atherosclerotic plaque is gaining increasing recognition but the mechanisms are not yet fully understood. The aim of this study was to investigate the significance of MMP-3 in the acute phase of myocardial infarction (MI) and the influence of the -1612 5A/6A MMP-3 gene promoter polymorphism on serum MMP-3 concentration. SUBJECTS: One-hundred and sixty-four patients admitted with ST-elevation MI and receiving thrombolysis treatment were included in this study. Serum MMP-3 was analysed at admission, after 48 h and at 3 months. RESULTS: Serum MMP-3 concentration was significantly increased at 3 months when compared with admission and 48 h (19.5 ng mL(-1) [14.4-24.7] vs. 15.5 ng mL(-1) [10.5-21.8] at admission, P < 0.001; and 14.7 ng mL(-1) [9.9-23.8] at 48 h, P < 0.001). Furthermore, we found the -1612 5A/6A polymorphism to influence the serum concentration of MMP-3 at all time-points: 14.1 ng mL(-1) [10.2-18.8] in 5A/5A; 19.6 ng mL(-1) [15.0-24.4] in 5A/6A; and 24.0 ng mL(-1) [20.1-32.3] in 6A/6A genotype at 3 months (P < 0.001 between all groups). Female patients had lower serum MMP-3 concentration than male patients at all time-points (14.8 ng mL(-1) [9.4-20.8] vs. 19.9 ng mL(-1) [16.0-26.9], P < 0.0001 at 3 months). CONCLUSIONS: Serum concentration of MMP-3 is significantly lower in the acute stage of MI than during recovery and is significantly influenced by -1612 5A/6A genotype and gender. Together with previous findings, these results primarily implicate MMP-3 in atherosclerosis progression rather than in acute MI.

Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 -1612 5A/6A promoter genotype and associated with myocardial infarction.

OBJECTIVES: Matrix metalloproteinase-3 (MMP-3) is implicated in the formation of atherosclerotic plaques, and the MMP-3 -1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the -1612 5A/6A polymorphism in the promoter region of the MMP-3 gene influences serum concentrations of MMP-3 and whether serum concentrations of MMP-3 are related to extent of coronary atherosclerosis and risk of MI. DESIGN AND SUBJECTS: This case-control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty-seven sex- and age-matched control subjects were recruited from the general population of the same county. METHODS: The MMP-3 genotype was determined by Pyrosequencing(TM) and the serum MMP-3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n=243). RESULTS: Patients had lower serum MMP-3 concentration than controls. There was a strong association between MMP-3 -1612 5A/6A genotype and serum concentrations of MMP-3. The presence of one or two copies of the 6A-allele was associated with a graded increase in serum MMP-3. In female patients there was an inverse correlation (r=-0.39, P<0.05) between serum MMP-3 concentration and plaque area. Conclusion. In conclusion, the serum concentration of MMP-3 is influenced by MMP-3 -1612 5A/6A genotype and associated with MI.

Prognostic value of plasma C-reactive protein and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis.

OBJECTIVES: To investigate the prognostic value of plasma C-reactive protein (CRP) and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients aged 75 years or below, treated with thrombolysis because of typical symptoms of myocardial infarction and electrocardiogram showing ST-segment elevation or bundle branch block were included in the study. The patients were followed for 24-60 months (mean 40 +/- 16 months). MAIN OUTCOME MEASURES: Cardiovascular death or new myocardial infarction. RESULTS: Concentrations of CRP were significantly higher at 48 h than at 3 months, whilst the levels of fibrinogen were similar. CRP and fibrinogen concentrations measured during the acute phase of myocardial infarction were associated with cardiovascular death or a new myocardial infarction during follow-up in univariate analysis. CRP levels measured 3 months after the acute event were not associated with subsequent events whereas fibrinogen concentrations showed a borderline prognostic significance (P = 0.05). When CRP and fibrinogen were entered into multivariate analysis together with the previously established prognostic factors in the patient group (age, diabetes mellitus and left ventricular function), these markers of inflammation did not add further prognostic information. CONCLUSION: C-reactive protein and fibrinogen do not carry the same independent prognostic information after acute myocardial infarction treated with thrombolysis as in studies previously reported for patients with unstable angina or non-Q-wave myocardial infarction.

Diabetes mellitus is a strong negative prognostic factor in patients with myocardial infarction treated with thrombolytic therapy.

OBJECTIVES: To assess the long-term prognostic values of baseline demographic data, occurrence of vectorcardiographic signs of reperfusion, left ventricular function and coronary angiographic features. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients (mean age 61 years) with a suspected acute myocardial infarction treated with thrombolysis were investigated and followed for 2-5 years (mean 1216 days). MAIN OUTCOME MEASURES: Death or a new myocardial infarction. RESULTS: Age above 55 years (P < 0.05), a previous diagnosis of diabetes mellitus (P < 0.005), hypertension (P < 0.05), heart failure (P < 0.001) and myocardial infarction (P < 0.05), a previous use of beta-blockers (P < 0.05) and an ejection fraction below 60% (P < 0.01) were predictors for death or a new myocardial infarction in univariate analysis. Sex, a previous history of smoking or angina pectoris, vectorcardiographic signs of reperfusion or degree of coronary artery disease had no prognostic values. In multivariate analysis including age above 55 years, a previous diagnosis of diabetes mellitus, hypertension and myocardial infarction, and an ejection fraction below 60%, only age (P < 0.05), diabetes mellitus (P < 0. 01) and ejection fraction (P < 0.05) were predictors for death or a new myocardial infarction. CONCLUSIONS: The results of the present study emphasize the importance of diabetes mellitus as a long-term prognostic risk factor in patients with myocardial infarction treated with thrombolysis. Further studies are needed to determine the mechanisms behind this increased risk.

Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment.

OBJECTIVES: We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment. METHODS: The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements. RESULTS: Bezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis. CONCLUSIONS: IGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.

Accumulation of apolipoprotein C-I-rich and cholesterol-rich VLDL remnants during exaggerated postprandial triglyceridemia in normolipidemic patients with coronary artery disease.

BACKGROUND: Exaggerated postprandial triglyceridemia is common in normolipidemic patients with coronary artery disease (CAD). Alterations in the composition of triglyceride-rich lipoproteins (TRLs) are likely to underlie this metabolic disturbance. However, the composition of very-low-density lipoproteins (VLDLs), which are the most abundant postprandial TRLs, has never been defined in CAD patients. METHODS AND RESULTS: We examined postprandial changes in the number and composition of VLDLs in middle-aged, normolipidemic CAD patients and control subjects. TRLs from 14 patients and 14 control subjects aged 45 to 55 years were subfractionated by density gradient ultracentrifugation into Svedberg flotation rate (Sf) fractions >400, 60 to 400, and 20 to 60. The VLDLs were separated from chylomicron remnants by immunoaffinity chromatography. In CAD patients, the postprandial concentrations of triglycerides and large (Sf 60 to 400) VLDL particles were elevated. In addition, their postprandial large VLDLs were enriched in apolipoprotein (apo) C-I and their postprandial small (Sf 20 to 60) VLDL remnants were enriched with apo C-I and cholesterol. CONCLUSIONS: Perturbed handling of postprandial triglycerides in normolipidemic CAD patients involves the accumulation of apo C-I-rich large VLDL particles and the generation of small, apo C-I- and cholesterol-rich VLDL remnants.

Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

OBJECTIVES: To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment. METHODS: A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography. RESULTS: In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression. CONCLUSIONS: Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.

Emotional distress before coronary bypass grafting limits the benefits of surgery.

BACKGROUND: The inclusion of large, heterogeneous groups of patients for coronary bypass grafting (CABG) surgery has resulted in a more mixed treatment outcome. Thus it becomes important to identify patients who are less likely to benefit from surgery or who may require additional support to improve treatment outcome. The aim of the present study was to examine whether psychological status measured before CABG can contribute to prediction of short- and long-term outcomes of the surgery. METHODS AND RESULTS: One hundred seventy-one consecutive patients from two large university hospitals in Stockholm completed a psychosocial questionnaire before being scheduled for surgery. One year after CABG, patients again completed the questionnaire. Follow-up of medical charts was conducted during the first 3 years after surgery. All major cardiac events (cardiac death, definite myocardial infarction, revascularization, and unstable angina verified by angiography or myocardial scintigraphy) were recorded. Although the overall effect of surgery was excellent in the majority of cases, the patients exhibiting a high degree of distress (anxiety, depression, and tiredness) before surgery assessed their status as being much worse both before the operation and at the 1-year follow-up. Equally important was the fact that patients considered distressed before surgery had significantly higher rates of cardiac events (16%) in the 3-year follow-up period compared with nondistressed patients (5%) (chi-square=5.11, degrees of freedom=1, p < 0.02). CONCLUSIONS: Systematic evaluation and treatment of emotional distress in the candidates for coronary revascularization may be expected to result in more optimal subjective results and a reduction in the number of serious cardiac events after surgery.

Results of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and an update on trials now in progress.

Bezafibrate is a latest generation fibrate derivative that substantially reduces total plasma cholesterol and triglyceride concentrations and increases high density lipoprotein (HDL) cholesterol. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was a double-blind, placebo-controlled trial over 5 years to assess the angiographic benefits of bezafibrate retard (400 mg. day (-1) in young, male, post-myocardial infarction (post-MI) patients. The trial demonstrated that without lowering serum low density lipoprotein cholesterol, progression of coronary atherosclerosis was prevented and the coronary event rate reduced. In subgroup analyse, bezafibrate decreased the rate of progression of coronary atherosclerosis and coronary event rate in young post-MI patients, primarily by slowing the progression of mild-to-moderate lesions. Additional studies are underway to explore further the benefits of this fibrate in coronary heart disease. The Bezafibrate Infarction Prevention study is the first trial to investigate the effects of raising HDL cholesterol and lowering triglycerides in patients with established coronary disease. The Lower Extremity Arterial Disease Event Reduction study is assessing the benefit of lowering fibrinogen in the prevention of major ischaemic heart disease and stroke in patients with peripheral vascular disease.

Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and degree of coronary artery disease.

OBJECTIVES: To determine the prevalence of chronic infection with Helicobacter pylori (HP) in patients with established coronary artery disease (CAD) and in healthy controls. Furthermore, to investigate whether HP infection is associated with inflammatory parameters, lipid concentrations and degree and progression of CAD. DESIGN: A case-control study combined with a prospective angiographic study. SETTING: Stockholm Metropolitan Area, Sweden. PATIENTS AND METHODS: A material consisting of 92 young men aged 40.9 +/- 3.2 (mean +/- SD) years, with previous myocardial infarction and documented coronary atherosclerosis, and 95 healthy sex-matched controls, aged 43.2 +/- 3.0 (mean +/- SD) years, with similar socio-economic status and ethnic background was analysed for the prevalence of HP seropositivity, plasma concentrations of the inflammatory parameters fibrinogen, tumour necrosis factor alpha and orosomucoid, and serum concentrations of lipids. The impact of HP seropositivity on degree and progression of CAD, as assessed by quantitative coronary angiography, was also determined. RESULTS: The study population of mainly Scandinavian origin had a low prevalence of HP seropositivity in comparison with previously published European populations. No significant increase in HP seropositivity was found in patients compared with controls (42.2 vs. 32.6%). Furthermore, HP infection was not associated with increased levels of inflammatory parameters, lipid concentrations or with degree of angiographically determined CAD at baseline, or progression of CAD and clinical events over 5 years. CONCLUSIONS: HP infection is not associated with inflammatory parameters and lipid concentrations and could not be confirmed as a risk factor for CAD.

Evidence for a role of tumor necrosis factor alpha in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease.

Elevated plasma levels of triglyceride-rich lipoproteins, a decreased high-density lipoprotein (HDL) cholesterol concentration, hyperinsulinemia, and impaired fibrinolytic function frequently aggregate in patients with premature coronary heart disease (CHD). Experimental studies suggest that the cytokine tumor necrosis factor alpha (TNFalpha) produced by adipocytes plays a part in the regulation of triglyceride and glucose metabolism. The present study examined whether TNFalpha is implicated in these metabolic and fibrinolytic disturbances in young postinfarction patients. TNFalpha levels were determined in two groups of young (age <45 years) male postinfarction patients (n = 92 and 60) and in matched, population-based control subjects (n = 63). Plasma TNFalpha was higher in patients than in controls (4.1 +/- 1.6 v2.5 +/- 0.4 pg/mL, P < .0001). In hyperlipidemic patients, TNFalpha levels correlated significantly with the concentrations of very-low-density lipoprotein (VLDL) triglyceride and cholesterol and negatively with HDL cholesterol. Treatment with bezafibrate decreased VLDL triglycerides and increased HDL cholesterol, but did not affect TNFalpha levels. The TNFalpha concentration also correlated significantly with fasting glucose and proinsulin concentrations, as well as glucose and proinsulin levels after glucose ingestion. In contrast, no relations were found with the insulin level or degree of insulin resistance. The present results provide clinical evidence for a basic role of TNFalpha in hypertriglyceridemia, glucose intolerance, and the etiology of premature CHD.

Effect of bezafibrate treatment over five years on coronary plaques causing 20% to 50% diameter narrowing (The Bezafibrate Coronary Atherosclerosis Intervention Trial [BECAIT]).

Recent reports indicate that most coronary events originate from plaques causing <50% diameter stenosis. A subgroup analysis of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) data was undertaken to determine the effects of bezafibrate in relation to baseline narrowing. BECAIT included 92 male postacute myocardial infarction patients <45 years of age. Each received double-blind treatment with bezafibrate (200 mg 3 times daily) or placebo for 5 years, together with a low-fat diet. Coronary angiography was performed at baseline and after 2 and 5 years. The mean minimum lumen diameter of lesions causing 20% to <50% diameter stenosis at baseline did not narrow over 5 years in the bezafibrate group and decreased by 0.15 mm in the placebo group (p <0.05). In segments with > or =50% diameter stenosis at baseline, no change was seen in either of the 2 groups. In the analysis including only segments with 20% to <50% stenosis at baseline, coronary events were seen in 7 of 40 patients with a progression in minimum lumen diameter of more than the median value and in 3 of 41 patients with a change less than the median value. Thus, bezafibrate had a preferential effect in slowing the progression of narrowings causing <50% stenosis at baseline in young men followed up for a 5-year period after acute myocardial infarction.

Retardation of coronary atherosclerosis: the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and other angiographic trials.

A large number of both primary and secondary preventive trials suggest that treatment of elevated plasma lipids may reduce the frequency of coronary heart disease (CHD) events. Meta-analyses indicate that for every 10% reduction of cholesterol, CHD mortality is lowered by 13% and all-cause mortality by 10%. Experience from several angiographic trials also suggests that coronary atherosclerosis can be retarded, and in some instances limited regression induced, by low-density lipoprotein (LDL)-cholesterol reduction and/or high-density lipoprotein (HDL)-cholesterol elevation. Coronary angiographic studies have shown that although the effects on retardation/regression of altherogenic lesions have been small, with luminal diameter changes of around 0.10 mm, the effects on clinical events were more substantial, with reductions of the order of 50%. There is also evidence that it is the mild and moderate lesions that are of particular concern with respect to the occurrence of clinical coronary events. The progression of atherosclerosis and the occurrence of coronary events are probably not exclusively dependent on a lowering of LDL-cholesterol concentrations. Analyses from the Monitored Atherosclerosis Regression Study (MARS), the Cholesterol Lowering Atherosclerotic Study (CLAS), and the Programs on the Surgical Control of the Hyperlipidaemias (POSCH) indicate that triglyceride-rich lipoproteins may also be of importance for the progression of mild/moderate lesions in subjects treated with cholesterol-lowering regimens. Recently, the results of the 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) demonstrated that bezafibrate significantly retarded the progression of coronary atheroma and coronary events in young male survivors of myocardial infarction, as assessed by changes in minimum lumen diameter. This positive outcome is most likely due to the beneficial treatment effects on the levels of serum triglycerides (-31%), plasma fibrinogen (-12%), and HDL cholesterol (+9%). The results of the BECAIT on progression of coronary atherosclerosis are comparable with those of two recent angiographic trials with HMG-CoA reductase inhibitors, the Multicenter Anti-Atheroma Study (MAAS), and the Regression Growth Evaluation Statin Study (REGRESS), despite different lipid and metabolic effects. BECAIT is the first controlled angiographic study to show that a fibrate can significantly retard the progression of coronary atherosclerosis. The exact mechanisms by which this occurs remain to be elucidated. However, the results of BECAIT illustrate the importance of factors other than LDL cholesterol in the progression of coronary atherosclerosis.

Secondary preventive potential of lipid-lowering drugs. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

Current experience from coronary angiographic trials using different treatment regimens such as lifestyle changes, resins, nicotinic acid and statins, shows that progression of atheroma can be retarded, and that regression can sometimes be induced, by a marked lowering of LDL-cholesterol. Young post-myocardial infarction patients, however, usually exhibit a multiplicity of metabolic risk factors with dyslipidaemias, predominantly hypertriglyceridaemia, and disturbances of glucose-insulin homeostasis and of the haemostatic system. These factors, together coupled with coronary angiographic data showing that the degree of dyslipidaemia is related to the extent and degree of coronary atherosclerosis, and the fact that rapid progression of coronary atherosclerosis was foreseen in this group of patients, resulted in the initiation of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in 1985. BECAIT was a 5-year, double-blind, placebo-controlled study of bezafibrate (200 mg three times daily) and dietary intervention in dyslipidaemic male survivors of myocardial infarction below 45 years of age. The angiographic analysis included 81 patients (42 bezafibrate and 39 placebo) who underwent baseline and at least one post-treatment angiogram, at 2 and 5 years. Changes in mean minimum lumen diameter indicated that there was 0.13 mm less (95% Cl: 0.10; 0.15) disease progression in focal lesions in the bezafibrate group than in the placebo group (P = 0.049). Parallel, but non-statistically significant, treatment effects were observed for mean segment diameter and percent stenosis. Three patients treated with bezafibrate and 11 patients in the placebo group suffered coronary events during the course of the trial (P = 0.02 logrank test). The angiographic effects of bezafibrate were accompanied by statistically significant reductions in serum cholesterol and triglycerides. Furthermore, plasma fibrinogen levels were significantly reduced and HDL-cholesterol concentration increased but there was no net change in LDL-cholesterol. These findings show that bezafibrate slowed the progression of focal coronary atherosclerosis to a degree that is comparable to that achieved with the statins in angiographic trials such as MAAS and REGRESS. Bezafibrate also reduced the occurrence of coronary events in young post-infarction victims. Like BECAIT, analyses of data from the NHLBI type II study, CLAS, POSCH and MARS provide evidence for the role of triglyceride-rich lipoproteins in the progression of coronary artery disease. Retardation of progression of atherosclerosis and a reduction in coronary events is, therefore, possible without reducing LDL-cholesterol.

Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients.

BACKGROUND: Bezafibrate has effects on lipid metabolism and haemostatic function. We undertook a double-blind, placebo-controlled intervention trial, the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), to establish whether bezafibrate (200 mg three times daily) could retard or prevent the progression of atherosclerotic lesions in dyslipidaemic male survivors of myocardial infarction who were younger than 45 years at the time of the event. METHODS: 92 patients completed an initial 3-month period of dietary intervention and were randomly assigned to treatment with bezafibrate or placebo. Dietary intervention continued throughout the trial. Coronary angiography was done at baseline and after 2 and 5 years. 81 patients (42 bezafibrate treated and 39 placebo treated) who underwent baseline angiography and at least one post-treatment angiogram were included in the efficacy analysis. The primary endpoint was change in mean minimum lumen diameter. FINDINGS: The mean minimum lumen diameter decreased from baseline to the last angiographic assessment (2 or 5 years) by 0.06 mm (95% CI 0.15 reduction to 0.01 increase) in the bezafibrate group and by 0.17 mm (0.33 reduction to 0.09 increase) in the placebo group. The treatment effect was therefore 0.13 mm (95% CI 0.10 to 0.15; p=0.049). Parallel treatment effects, although not statistically significant, were observed for the secondary angiographic endpoints (mean segment diameter 0.02 mm [0.01-0.04] and percentage stenosis -3.41% [-4.00 to -2.98]). The cumulative coronary event rate was significantly lower among bezafibrate-treated than among placebo-treated patients (three vs 11 patients; p=0.02). There were significant treatment effects of bezafibrate for serum concentrations of cholesterol (-9%; p<0.001), very-low-density-lipoprotein (VLDL) cholesterol (-35%; p<0.001), serum triglycerides (-31%; p<0.001), VLDL triglycerides (-37%; p<0.001), and plasma fibrinogen (-12%; p=0.001), whereas low-density (LDL) cholesterol concentrations did not change. High density lipoprotein (HDL) cholesterol increased significantly with bezafibrate (9%; p=0.02). INTERPRETATION: The results show that bezfibrate improves dyslipidaemia, lowers plasma fibrinogen, slows the progression of focal coronary atherosclerosis, and reduces coronary events in young survivors of myocardial infarction.

Design features of a five-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

Young survivors of myocardial infarction represent a poignant challenge to clinical research on atherogenic mechanisms and factors predisposing to and precipitating coronary thrombosis. Young male postinfarction patients are characterized by heavy smoking, dyslipoproteinaemias involving very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), a family history of premature coronary artery disease, hyperinsulinaemic responses to oral and intravenous glucose challenges, an elevated plasma fibrinogen concentration and defective fibrinolytic function. Based on the multiplicity of metabolic and haemostatic disturbances present in these patients, a double-blind, randomized, placebo-controlled angiographic trial was initiated to determine whether bezafibrate, a clofibrate analogue, retards the progression or facilitates regression of premature coronary atherosclerosis. Men under the age of 45 years who survived a first myocardial infarction were screened for participation in the study. A fasting serum cholesterol value > or = 5.2 mmol/l and/or serum triglycerides > or = 1.6 mmol/l after three months of dietary treatment and angiographically demonstrable lesions in at least one coronary segment were required for inclusion. Treatment with diet and bezafibrate (200 mg t.i.d.) or matching placebo is continued for five years during which time re-angiography is performed after two years and at the end of the study. The primary aim of the trial is a comparison between the bezafibrate and placebo groups for change in mean minimum luminal diameter between the baseline and five-year coronary angiograms. This report presents the design features of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and a review of current knowledge of mechanisms underlying premature coronary atherosclerosis and myocardial infarction at a young age.

Coronary angiographic changes during 2 years after myocardial infarction largely undetected by repeated tomographic thallium-201 scintigraphy and not reflected by clinical symptoms.

Repeated coronary angiographies and single photon emission computed tomographies (SPECT) were performed at 9 and 33 months after myocardial infarction (MI) in 47 young men. Coronary lesions were classified in eight grades with respect to the reduction of the luminal diameter. The progression and regression of two steps or more in lesions of grade 2 or more, the recanalization of coronary thrombosis and an increase in collaterals were recorded. Patients were divided into three groups with regard to (A) deterioration, (B) improvement and (C) no changes in the three major coronary regions, respectively. Overall, 23 patients (49%) showed changes between the first and the second investigation. A simplified method using summarized short-axis slices for evaluation of the thallium-201 SPECT showed a significant difference in change of regional myocardial uptake of thallium-201 between groups A and B (P = 0.047) but not between the groups A and C, in lateral myocardial regions. No significant differences were found between any of the groups in respect of the anterior or inferior myocardial regions. These findings were not explained by changes in clinical status, maximum heart rate or workload, or by changes in medication. Our results suggest that substantial changes in coronary morphology can take place during the 2 years following MI without consistent changes in clinical symptoms or regional myocardial perfusion.

Does diffuse coronary atherosclerosis affect the relation between coronary stenoses and uptake of thallium-201 after exercise?

It has been proposed that diffuse coronary atherosclerosis influences the myocardial perfusion. We performed a study of 94 young men with previous myocardial infarction in order to find out whether the presence and extent of diffuse coronary atherosclerosis affected the relation between maximal stenosis and myocardial perfusion in areas remote from the infarction. The patients were examined by planar-imaging thallium-201 scintigraphy, following exercise, and coronary angiography within 6 months after myocardial infarction. The maximal distinct stenosis and diffuse coronary atherosclerosis, comprising both plaque size and extent, were semiquantitatively assessed. The correlation coefficients between maximal stenosis within the LAD, RCA, and LCX vascular territories and the corresponding initial uptake of thallium were 0.52 (P = 0.0001), 0.30 (P = 0.04), and 0.46 (P = 0.02), respectively. No change of the correlations was found, except for a slight increase of the r-value from 0.30 to 0.37 in regions corresponding to RCA, after controlling for the diffuse atherosclerosis score in a multiple stepwise regression analysis. These findings indicate no impact of diffuse coronary atherosclerosis on regional myocardial perfusion in areas remote from the infarction.

Two-year survival after myocardial infarction.

We have studied 773 consecutive cases (706 individuals) with definite myocardial infarction treated in the Coronary Care Unit at Danderyd Hospital in Stockholm during the period 1984-85. Hospital mortality was 12.9% in all patients and 8.9% in patients under 70 years of age. Six hundred and six patients were discharged from the hospital and followed up for 2 years. The 2-year mortality in ischaemic heart disease was 14.4% in all patients and 9.5% in patients under 70 years of age and, including all causes of death, 20.3% and 14.6%, respectively. Our policy for medical treatment included frequent use of beta-adrenergic blocking agents, even in heart failure, and restricted use of antiarrhythmic drugs and digitalis. A short delay of admission may have been beneficial for the result of different kinds of anti-ischaemic intervention. Furthermore, a routinely performed exercise ECG before discharge and after 6 weeks, as part of a structured follow-up, has improved our ability to detect complications at an early stage and to optimize medical treatment.